Drug delivery and substance transfer facilitated by nano-enhanced device having aligned carbon nanotubes protruding from device surface

ABSTRACT

The present invention relates to a nano-enhanced device for substance transfer between the device and a tissue. The device comprises a substrate with substantially aligned carbon nanotubes anchored within the substrate, and with at least one end of the carbon nanotubes protruding from the substrate. The protruding nanotube ends may be coated with a drug for delivery of the drug into body tissue. The present invention may be incorporated into an angioplasty catheter balloon or into a patch that is worn on the skin. The carbon nanotubes can be grouped in clusters to effectively form nano-needles which can transfer fluid to or from the subdermal tissue. The nano-needles can be used in conjunction with a sensor to ascertain body fluid information such as pH, glucose level, etc.

PRIORITY CLAIM

This application is a divisional of U.S. patent application Ser. No.13/762,197, filed Feb. 7, 2013, entitled “DRUG DELIVERY AND SUBSTANCETRANSFER FACILITATED BY NANO-ENHANCED DEVICE HAVING ALIGNED CARBONNANOTUBES PROTRUDING FROM DEVICE SURFACE,” which is a continuation ofU.S. patent application Ser. No. 12/657,862, filed on Jan. 27, 2010,entitled “DRUG DELIVERY AND SUBSTANCE TRANSFER FACILITATED BYNANO-ENHANCED DEVICE HAVING ALIGNED CARBON NANOTUBES PROTRUDING FROMDEVICE SURFACE,” all of which are incorporated by reference in theirentirety. U.S. patent application Ser. No. 12/657,862 also claimspriority to U.S. Provisional Patent Appl. No. 61/179,639, filed May 19,2009, entitled “METHOD, DEVICE AND DESIGN FOR DELIVERY OF DRUGS BY ANANO-ENHANCED ANGIOPLASTY BALLOON,” and U.S. Provisional Patent Appl.No. 61/206,071, filed Jan. 27, 2009, entitled “CARBON NANOTUBE-BASEDDEVICE FOR SUB-DERMAL BLOOD AND FLUID PROPERTY MONITORING”. U.S. patentapplication Ser. No. 12/657,862 is also a continuation-in-part of U.S.patent application Ser. No. 11/827,169, filed Jun. 10, 2007, now U.S.Pat. No. 7,955,644, entitled “METHOD FOR SELECTIVELY ANCHORING LARGENUMBERS OF NANOSCALE STRUCTURES.”

FIELD OF THE INVENTION

The present invention relates to a nanostructure-enhanced drug deliveryand blood monitoring device and, more particularly, to a device withaligned carbon nanotubes protruding from the device surface forfacilitating drug or fluid transfer between the device and body tissue.

BACKGROUND OF THE INVENTION

Microvasculatures in the sub-dermal layer, if accessed, provide vitalinformation about the health of the measured individual. For example,blood-glucose level, oxygen content, hormonal concentration, etc., canbe directly measured from blood properties. Often to achieve thisinformation, the skin must be penetrated by a needle in order to drawthe blood into a sampling device. Use of such a needle is typicallyassociated with pain, exposure of the blood to the environment, or riskof infection due to the rupture of the skin. A less invasive alternativeto this procedure is to have a sensor embedded within the sub-dermallayer. Again, this procedure (depending on the scale) to achieve theimplant is problematic both due to the process of placing the implantand the potential rejection by the patient's body.

Another area relevant to the subject matter of the present invention isin angioplasty procedures. Percutaneous transluminal angioplasty (PTA)and percutaneous transluminal coronary angioplasty (PTCA) areestablished, proven methods for re-opening stenotic or occluded arteriesin a minimally invasive way. A balloon is placed in the stenotic segmentof the artery using a catheter and then expanded until the lumen reachesits desired diameter. The use of an expanded balloon to forcibly openthe narrowed section of the artery requires very high pressure (15 bars)and tends to cause injury to the vessel walls. The body's naturalresponse to such injury is hyperproliferation, an abnormally high rateof cell division, which results in lumen narrowing and thus decreasedfunction of the vessel. This is counterproductive to the initial goal ofopening the stenotic or occluded artery.

To counter the hyperproliferation response of the vessel, anantiproliferative taxane drug such as paclitaxel may be used. A single,short contact of tissue with a small dose of paclitaxel has been shownto inhibit local cell proliferation. Paclitaxel is a mitotic inhibitoroften used in cancer chemotherapy because cancerous cells exhibithyperproliferation. Paclitaxel was originally derived from the bark ofPacific yew trees, but is now produced from other bioengineeringmethods. The mechanism of action of paclitaxel is the stabilization ofmicrotubules through binding to tubulin, thus interfering with theirnormal breakdown during cell division. This has the net effect ofreduced cell division rates, and counteracts hyperproliferation.

Antiproliferative taxanes have important properties for minimizing thehyperproliferation response of damaged vessel walls. They have highlipophilicity (hydrophobicity) and bind tightly to various cellconstituents, giving good local retention at the delivery site. Thoughhydrophilic compounds penetrate easily into tissues, they also clearquickly. Paclitaxel is a hydrophobic compound and diffuses into thearterial wall from the lumen where it is delivered (See LiteratureReference No. 1).

A typical procedure for treating a stenotic or occluded artery is to usea paclitaxel-coated angioplasty balloon, with the paclitaxel serving itspurpose of inhibiting hyperproliferation following the balloon openingprocess. The major limitations on this process are the following:

1. The need of long inflation time in order to make sure the paclitaxeldiffusion to the arterial wall is sufficient, which may cause excessivearterial wall injury. Previous study shows that 40-60 minutes arerequired to transfer roughly 90% of the initial dose of paclitaxel tothe arterial wall (See Literature Reference No. 1);

2. In order to obtain the optimum benefit of hyperproliferationinhibition, it is important that the paclitaxel coating is not lost orwashed off by the blood stream while advancing into the stenotic segmentof the artery. Previous study shows that the rate of paclitaxel beingwashed away from the uninflated balloon by the blood stream is up to1.2% from the initial dose per minute (See Literature Reference No. 2);

3. Potential loss of paclitaxel coating due to contact with the healthyarterial wall while advancing into the stenotic segment of the artery;and

4. The maximum dose of paclitaxel that can be applied on a singleballoon is around 11 mg (10 μg/mm²), which is significantly less thanthe paclitaxel dose approved by the FDA for Taxol (See LiteratureReference No. 1).

It should be noted that the use of carbon nanotubes for the purpose ofreinforcing the material properties of a balloon catheter has beensuggested in U.S. Pat. No. 7,037,562. However, in that patent, thecarbon nanotubes were mixed with the base material for the purpose ofstrengthening the material and not for drug delivery purposes. Inaddition, the carbon nanotubes were not aligned or partially anchored inthe base material in a way such that they would protrude from thesurface and facilitate drug delivery, rendering the devicenon-functional for that purpose.

Thus, a continuing need exists for a minimally invasive blood monitoringdevice which protects the extracted fluid from the atmosphere, and alsofor a drug delivery system which can effectively deliver high amounts ofa desired drug to an affected site in a relatively short time periodwith minimal drug loss to passing body fluids.

The following references are cited throughout this application. Forclarity and convenience, the references are listed herein as a centralresource for the reader. The following references are herebyincorporated by reference as though fully included herein. Thereferences are cited in the application by referring to thecorresponding literature reference number.

(1) Creel, C. J., M.A. Lovich, and E. R. Edelman, Arterial paclitaxeldistribution and deposition. Circulation Research, 2000. 86(8): p.879-884.

(2) Scheller, B., U. Speck, C. Abramjuk, U. Bernhardt, M. Bohm, and G.Nickenig, Paclitaxel balloon coating, a novel method for prevention andtherapy of restenosis. Circulation, 2004. 110(7): p. 810-814.

(3) Bronikowski, M. J., Longer nanotubes at lower temperatures: Theinfluence of effective activation energies on carbon nanotube growth bythermal chemical vapor deposition. Journal of Physical Chemistry C,2007. 111(48): p. 17705-17712.

SUMMARY OF INVENTION

The present invention relates to a nano-enhanced device for substancetransfer between the device and a tissue. In one aspect, the devicecomprises a substrate and an array of substantially aligned carbonnanotubes having two ends, the carbon nanotubes being anchored withinthe substrate with at least one end protruding from the substrate,whereby the protruding carbon nanotubes enhance the substance transfercapabilities of the device.

In another aspect of the device, the carbon nanotube array is coatedwith a substance selected from the group consisting of a drug and agene.

In yet another aspect of the device, the protruding ends of the anchoredcarbon nanotubes are free of coated drug and the drug coating areaconsists of an area selected from the group consisting of side walls ofthe carbon nanotubes and free spaces between the carbon nanotubes.

In another aspect, the device type is selected from the group consistingof a patch to be worn on the tissue and an angioplasty balloon.

In a further aspect of the device, the coated drug is paclitaxel.

In another aspect of the device, delivery of the drug from the device tothe tissue is enhanced by a method selected from the group consisting ofdirect or indirect heating of at least a portion of the carbon nanotubearray, electrical current through at least a portion of the carbonnanotube array, laser or other optical stimulation of at least a portionof the carbon nanotube array, ultrasonic waves on at least a portion ofthe carbon nanotube array, mechanical vibration of at least a portion ofthe carbon nanotube array, and modifying the hydrophobicity of thenanotube array during fabrication.

In yet another aspect, the drug delivery enhancement is executed at atime selected from the group consisting of instantly and according to atimed sequence.

In another aspect of the device of the present invention, the carbonnanotubes are arranged in one or more clusters, such that each clustereffectively functions as a needle.

In another aspect of the device, the substrate comprises a porousmaterial, whereby substances may be transferred to or from the deviceand the tissue via inherent capillary action of the carbon nanotubes.

In another aspect, the porous substrate material is loaded with asubstance to be transferred to the tissue via the carbon nanotubes.

In yet another aspect of the device, the carbon nanotube clusters arepatterned in a manner such that they are electrically isolated from oneanother, and where the device further comprises a sensor for readingelectrical potentials of the nanotube clusters.

In another aspect, the inherent electrical conductivity of the carbonnanotubes is modified by treatment of the carbon nanotubes with apre-coated chemical.

In a further aspect of the present invention, a subset of the carbonnanotube clusters is treated with glucose oxidase, and another subset ofthe carbon nanotubes is treated with ferric cyanide, whereby conductionthrough the blood may be achieved and allows for measurement of theblood-glucose level.

BRIEF DESCRIPTION OF THE DRAWINGS

The objects, features and advantages of the present invention will beapparent from the following detailed descriptions of the various aspectsof the invention in conjunction with reference to the followingdrawings, where:

FIG. 1 is a side view of a polymeric anchoring layer with carbonnanotubes protruding therefrom;

FIG. 2A is a side view of a nano-enhanced device according to thepresent invention, depicting the carbon nanotubes protruding from thesubstrate at only one end;

FIG. 2B is a side view of a nano-enhanced device according to thepresent invention, depicting the device piercing the surface of atissue;

FIG. 3A is a side view of a nano-enhanced device according to thepresent invention, depicting the carbon nanotubes as coated with a drugor agent;

FIG. 3B is a side view of a nano-enhanced device according to thepresent invention, depicting an interior portion of the carbon nanotubearray coated with a drug, but with the nanotube ends being left free ofthe coated drug;

FIG. 4A is a side view of a nano-needle anchored in a porous substratematerial in accordance with the present invention;

FIG. 4B is a side view of a device having multiple nano-needlesprotruding therefrom;

FIG. 5A is a side view of a nano-enhanced device connected with a sensorto form a nano-probe;

FIG. 5B is a top view of a nano-probe device in accordance with thepresent invention where the nano-needle clusters are patterned intoelectrically isolated subsets;

FIG. 6A is an illustration showing a nano-enhanced catheter balloon inaccordance with the present invention, where the balloon is in adeflated state;

FIG. 6B is an illustration showing a nano-enhanced catheter balloon inaccordance with the present invention, where the balloon is in anexpanded state;

FIG. 7A is a perspective view of a nano-enhanced epidermal patch inaccordance with the present invention; and

FIG. 7B is an illustration showing a nano-enhanced epidermal patchadhered on the arm of a user.

DETAILED DESCRIPTION

The present invention relates to a nanostructure-enhanced drug deliveryand blood monitoring device and, more particularly, to a device withaligned carbon nanotubes protruding from the device surface forfacilitating drug or fluid transfer between the device and body tissue.The following description is presented to enable one of ordinary skillin the art to make and use the invention and to incorporate it in thecontext of particular applications. Various modifications, as well as avariety of uses in different applications will be readily apparent tothose skilled in the art, and the general principles defined herein maybe applied to a wide range of embodiments. Thus, the present inventionis not intended to be limited to the embodiments presented, but is to beaccorded the widest scope consistent with the principles and novelfeatures disclosed herein.

In the following detailed description, numerous specific details are setforth in order to provide a more thorough understanding of the presentinvention. However, it will be apparent to one skilled in the art thatthe present invention may be practiced without necessarily being limitedto these specific details. In other instances, well-known structures anddevices are shown in block diagram form, rather than in detail, in orderto avoid obscuring the present invention.

The reader's attention is directed to all papers and documents which arefiled concurrently with this specification and which are open to publicinspection with this specification, and the contents of all such papersand documents are incorporated herein by reference. All the featuresdisclosed in this specification, (including any accompanying claims,abstract, and drawings) may be replaced by alternative features servingthe same, equivalent or similar purpose, unless expressly statedotherwise. Thus, unless expressly stated otherwise, each featuredisclosed is one example only of a generic series of equivalent orsimilar features.

Furthermore, any element in a claim that does not explicitly state“means for” performing a specified function, or “step for” performing aspecific function, is not to be interpreted as a “means” or “step”clause as specified in 35 U.S.C. Section 112, Paragraph 6.

(1) Introduction

The present invention relates to a nanostructure-enhanced drug deliveryand blood monitoring device and, more particularly, to a device withaligned carbon nanotubes protruding from the device surface forfacilitating drug or substance transfer between the device and bodytissue.

Recent advances in carbon nanotube technology make it possible to createneedles or rods with diameters of the order of nanometers (nm) andlengths of the order of millimeters. Carbon nanotubes are beneficial inthe present application because the distribution of nerves within thedermal layers is sparse compared to nanoscale needles of size similar tocarbon nanotubes. For example, a collection of 200 carbon nanotubes withdiameters of 10 nm, in close contact, will occupy less than 2micrometers in total diameter for the whole collection. U.S. PatentApplication Publication No. 2008/0145616 Al describes a method forselectively anchoring a large number of nanoscale structures. Thisanchoring method allows control of the depth of anchoring the nanoscalestructures into the other material.

(2) Details of the Invention

Carbon nanotubes can be formed in several ways, the simplest beingthermal chemical vapor deposition using a catalyst-coated substrate.Typically a few nanometers of iron coated onto silicon, prepared inadvance and placed in a tube furnace under flow of carbon-containingfeedgas, such as ethylene, and elevated to a proper temperature, e.g.,725 degrees Celsius. Thermal chemical vapor deposition growth of carbonnanotubes (See Literature Reference No. 3) generates vertically alignedcarbon nanotubes on the growth substrate, which is typically silicon.

Anchoring an array of carbon nanotubes on a substrate can be done bybringing the array of carbon nanotubes into contact with a layer ofuncured polymer material and then undergoing a curing step, as describedin previously-cited U.S. Patent Application Publication No. 2008/0145616A1. In order to anchor carbon nanotubes into a tube-shaped substratesuch as a balloon material, a sacrificial release layer may be usedaround a central rod to keep a cylindrical shape. First, a sacrificialrelease layer is deposited and formed around the rod and possibly cured,and then the balloon material is deposited around the release layer. Thenanotubes are then attached or anchored into the balloon material.Finally, the sacrificial release layer is removed, releasing the balloonwith the nanotubes attached or anchoring into it.

Drugs, genes, or other substances may be coated onto carbon nanotubes inanother step, either before or after they are attached to the substrate.This is particularly enabled with the drug paclitaxel because it ishydrophobic, and carbon nanotubes are also hydrophobic in their as-grownstate. Thus, the paclitaxel molecules will prefer to adhere to thecarbon nanotubes until they are placed in close contact with occludingmaterials in vessels which are usually fatty and hydrophobic in nature.In addition, because the carbon nanotube surface is hydrophobic innature, any substance residing within the layer of nanotubes will beimmune from water and aqueous solutions and mixtures, such as blood,which come in contact with the nanotube surface. Thus, in a desiredaspect of the present invention, the tips of the carbon nanotubes areleft free of the drug coating, and the drug coating is limited to theside wall of the nanotubes and/or free spaces between nanotubes. Thisaspect provides a safe surface contact and also avoids premature drugrelease into non-target tissue or body fluid.

Drug release by the carbon nanotubes into the target tissue can beenhanced by connection with an enhancement device capable of performinga variety of enhancement methods, including but not limited to applyingone or more of the following to the carbon nanotubes: direct or indirectheating, for example, by electromagnetic radiation such as radiofrequency (RF) waves; electrical current; laser or other opticalstimulation; ultrasonic waves; mechanical vibration; and by modifyingthe hydrophobicity of the nanotube array during fabrication (this can bedone, for example, by treatment with oxygen plasma). These enhancementmethods can be applied to either a spatially patterned portion of or thecomplete set of the carbon nanotubes. The methods can also be appliedinstantaneously or according to a time sequence.

FIG. 1 is an illustration showing a generic embodiment of the presentinvention. The device comprises a substrate layer 100, and a pluralityof substantially aligned carbon nanotubes 102. Each carbon nanotube hastwo ends 104, and the carbon nanotubes 102 are anchored within thesubstrate 100 with at least one end 104 protruding from the substrate.In the example shown, the carbon nanotubes 102 protrude from thesubstrate 100 at both ends.

FIG. 2A illustrates another embodiment of the device, where the alignedcarbon nanotubes 102 protrude from the substrate 100 at only one end104. FIG. 2B shows the end 104 of a carbon nanotube array 102 piercingthe surface of a body tissue 200 such as skin, artery wall, colon, etc.It should be noted that the present invention has potential uses outsidethe medical field as well. The device could feasibly transfer substancesto a wide range of targets other than body tissue, and therefore is notlimited to that application.

The carbon nanotubes may be coated with a drug, a gene, or othersubstance to be transferred to the tissue. FIG. 3A illustrates anembodiment of the device where the carbon nanotubes 102 are coated witha substance 300 to be transferred to body tissue. In an alternateembodiment as shown in FIG. 3B, the ends 104 of the carbon nanotubes areleft free of the coated substance 300. The coated substance 300, in thiscase, would be limited to the side walls of the carbon nanotubes, and/orspaces between the carbon nanotubes.

(3.0) Specific Applications

(3.1) Needle

One aspect of the present invention is a device that uses a patterneddistribution of carbon nanotubes to function as a microscale needlewhich could easily penetrate dermal layers, reaching microvasculature orinterstitial fluids. Such a device could be used as a needle or reverseneedle to facilitate transfer of substances to and from the body,respectively. FIG. 4A shows a group of carbon nanotubes 102 anchoredinto a substrate 100 such that they form a nano-needle. In theembodiment shown, the substrate is porous 400. A two sided arrow 402shows the possible direction of migration of substances to or from thesubstrate via the carbon nanotubes 102. When functioning as a needle,blood or interstitial fluids are drawn into the porous substrate 400through sub-dermal contact of the carbon nanotube based needle with thefluid, similar to the piercing action shown in FIG. 2B. Analysis of thefluid is conducted through some separate means, such as by opticalanalysis. To function as a reverse needle, the porous substrate 400 ispre-loaded with some agent, for example, medication, which may then bedelivered via the carbon nanotube-based needle into the sub-dermalregion. FIG. 4B shows a device with multiple needle-like clusters ofnanotubes 102.

(3.2) Probe

The nano-needle device can be combined with a sensor to function as aprobe to monitor blood glucose levels or other blood or body fluidproperties, for example pH, sugar level, oxygen content, etc. The devicefunctions based on the inherent electrical conductivity of the carbonnanotubes. FIG. 5A is an illustration of a nano-probe according to thepresent invention. The probe comprises one or more clusters of carbonnanotubes 102 anchored in a substrate 100 in conjunction with a sensor500. The sensor may be operatively connected with the carbon nanotubes102 or with the substrate 100, or both, depending on the desired mode ofoperation. In FIG. 5A, the sensor 500 is operatively connected with thecarbon nanotube 102 clusters. In a desired embodiment as shown in thetop-view in FIG. 5B, the nanotube clusters are patterned in such amanner that they are electrically isolated from one another. The patternshown comprises an inner ring 502 and an outer ring 504 of nanotubeclusters. A specific use for the aspect shown in FIG. 5B is measuringblood glucose level. In this application, a subset of the carbonnanotube clusters (for example, the inner ring 502) is treated withglucose oxidase, while another subset of carbon nanotube clusters (forexample, the outer ring 504) is treated with ferric cyanide, wherebyconduction through the blood may be achieved and allows for measurementof the blood-glucose level. It should be noted that the presentinvention may employ many patterns of nanotube clusters in addition tothe specific embodiment shown in FIG. 5B. Furthermore, the device mayalso be used as a coated probe, where an agent such as a drug may bepre-coated onto the surface or within the carbon nanotubes as shown inFIGS. 3A and 3B, and thus delivered and released by penetration of thecarbon nanotubes into the body tissue.

(3.3) Paintbrush

An assembly of carbon nanotubes as shown in FIG. 4B can also act as awet paintbrush by virtue of the inherent capillary action of the carbonnanotubes. A similar method is described in U.S. patent application Ser.No. 11/124,523, which is hereby incorporated by reference as thoughfully set forth herein.

(3.4) Angioplasty Balloon

Another desired embodiment of the present invention is in angioplastyprocedures for delivering the drug paclitaxel for the preventionhyperproliferation of tissue cells following the inflation of theballoon to open a section of a blood vessel. However, the presentinvention should not be construed as limited to use in angioplastyprocedures or to delivery of paclitaxel. The present invention couldfeasibly be used to deliver a large variety of substances to variousparts of the body, including, but not limited to, the skin, uterus,bronchial tubes, and various portions of the gastrointestinal tractincluding colon.

FIGS. 6A and 6B illustrate a nano-enhanced angioplasty balloon 600according to the present invention. FIG. 6A shows the angioplastyballoon in deflated form, as it would be inserted into a blood vessel orother body enclosure. Upon inflation, as shown FIG. 6B, the surfacecarbon nanotubes 102 penetrate the blood vessel surface in the mannershown in FIG. 2B, releasing any drug coated thereon into the targettissue.

The present invention, with relation to use in angioplasty balloons,overcomes the limitations of the related art as described in theBackground section above, including long inflation time, reduced drugquantity available due to loss during insertions process, prematureand/or undesired delivery to healthy tissue, and a low total amount ofdrug delivered. Because the possible quantity of drug for delivery isdependent on surface area, the nano-enhanced balloon-catheter willretain more drug quantity though the insertion process and increase themaximum deliverable drug quantity by a factor on the order of 1000times, similar to the increase in surface area provided by thenanostructures.

The following expression compares the surface area of a nano-enhancedballoon with a standard balloon without nano-enhancement:

$\frac{A_{{nano} - {balloon}}}{A_{{standard} - {balloon}}} = {\frac{\frac{4\sqrt{3}\pi^{2}{dhRL}}{3\; s^{2}}}{2\pi\;{RL}} = \frac{2\sqrt{3}\pi\;{dh}}{3\; s^{2}}}$where:

-   d (106 in FIG. 1) is the diameter of an individual carbon nanotube;-   h (108 in FIG. 1) is the length of an individual carbon nanotube;-   s (110 in FIG. 1) is the distance between individual carbon    nanotubes;-   R (604 in FIG. 6B) is the radius of the balloon; and-   L (602 in FIG. 6A) is the length of the balloon, and    using the following assumed typical values:-   d=10 nm;-   s=100 nm; and-   h=500 nm,

${{the}\mspace{14mu}{following}{\mspace{11mu}\;}{result}\mspace{14mu}{is}\mspace{14mu}{obtained}\text{:}\mspace{14mu}\frac{A_{{nano} - {balloon}}}{A_{{standard} - {balloon}}}} = 1813.17$

This result indicates that the surface diffusion enhancement of acatheter balloon as described can easily increase the surface area by afactor of 10³.

(3.5) Epidermal Patch

The nano-enhanced surfaces of the present invention can be incorporatedinto an epidermal patch to be worn on the skin. FIG. 7A illustrates anexample of a nano-enhanced epidermal patch 700. The patch has alignedcarbon nanotubes 102 protruding from the surface to be adhered to theskin. A portion of the patch 700, for example the perimeter 702, may becoated with adhesive to facilitate adhesion to the skin. When the patch700 is applied to the skin as in FIG. 7B, the carbon nanotubes 102 willenter the skin in a manner shown in FIG. 2B and release any drug oragent coated thereon into the skin. The patch may be used in conjunctionwith any of the previously described embodiments of the presentinvention.

What is claimed is:
 1. A method of transferring a substance, comprising:(a) applying a device to a body of a patient, the device comprising asubstrate and an array of carbon nanotubes with each carbon nanotube inthe array having two ends, wherein the array of carbon nanotubes isanchored within the substrate with at least one end of each carbonnanotube protruding from the substrate, wherein the carbon nanotubeswithin the array are grouped in clusters such that each clustereffectively functions as a needle, wherein the clusters are arranged asa plurality of rings with all of the carbon nanotubes of the clustersbeing in a ring periphery, and wherein application of the device to thebody causes the clusters to enter tissue of the patient's body; and (b)allowing the transfer of the substance through the substrate and intothe tissue.
 2. The method of claim 1, wherein the substrate comprises aporous material and the substance is transferred into the tissue viainherent capillary action of the carbon nanotubes.
 3. The method ofclaim 1, wherein the substrate is loaded with the substance to betransferred to the tissue.
 4. The method of claim 1, wherein the carbonnanotubes are coated with the substance transferred to the tissue. 5.The method of claim 1, wherein the device is a patch comprising anadhesive, and wherein the patch is applied to the body of the patientsuch that the adhesive adheres to the body.
 6. The method of claim 5,wherein the adhesive coats only a perimeter portion of the patch withthe protruding nanotube clusters located on a portion interior to theperimeter portion.
 7. The method of claim 5, wherein the tissue isepidermal tissue.